Absorbable implants for plastic surgery

ABSTRACT

Absorbable implants for breast surgery that conform to the breast parenchyma and surrounding chest wall have been developed. These implants support newly lifted breast parenchyma, and/or a breast implant. The implants have mechanical properties sufficient to support a reconstructed breast, and allow the in-growth of tissue into the implant as it degrades. The implants have a strength retention profile allowing the support of the breast to be transitioned from the implant to regenerated host tissue, without significant loss of support. Three-dimensional implants for use in minimally invasive mastopexy/breast reconstruction procedures are also described, that confer shape to a patient&#39;s breast. These implants are self-reinforced, can be temporarily deformed, implanted in a suitably dissected tissue plane, and resume their preformed three-dimensional shape. The implants are preferably made from poly-4-hydroxybutyrate (P4HB) and copolymers thereof. The implants have suture pullout strengths that can resist the mechanical loads exerted on the reconstructed breast.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Ser. No. 14/813,454, filedJul. 30, 2015, which is a continuation U.S. Ser. No. 14/329,760, filedJul. 11, 2014, now U.S. Pat. No. 9,532,867, which claims the benefit ofand priority to U.S. Ser. No. 61/993,511 filed May 15, 2014 and U.S.Ser. No. 61/845,236, filed Jul. 11, 2013, all of which are incorporatedby reference in their entirety.

FIELD OF THE INVENTION

The present invention generally relates to absorbable implants that areshaped or have shaped memory so they can conform to anatomicalstructures or confer shape to anatomical structures, and are designedfor use in plastic surgery procedures.

BACKGROUND OF THE INVENTION

Numerous plastic surgery procedures are performed each year to restoreor correct the form or function of the body. Many of these proceduresseek to restore a youthful appearance, or even to enhance one's existingappearance. Natural factors, such as aging and gravity, contribute tothe loss of the youthful appearance. For example, skin laxity, loss ofmuscle tone, and attenuation of ligaments can result in ptosis(drooping) of the breast. Plastic surgeons have developed a plethora ofsurgical techniques to correct the ptosis of different anatomicalstructures that occurs with aging. These techniques vary in the type ofincision, direction of incision, plane of dissection, amount ofdissection, extent of repositioning of tissue, the use of differenttypes of sutures, different suturing techniques, and different fixationtechniques. Almost all of them rely on the use of the pre-existing skinenvelope as the support system for the newly lifted tissue. Theseapproaches almost invariably result in recurrent ptosis, since thesurgeon is merely relying on the aging and sagging surrounding tissuesthat have already failed to provide the necessary support to maintain anormal appearance. For example, de-epithelialization, flaptransposition, gland repositioning or suturing will not alter thephysical properties of the patient's tissue. At most, these techniquesonly slow recurrent ptosis by creating internal scars that providelimited reinforcement. And even the scarring process varies from patientto patient making this limited approach highly unpredictable. Notably,there is no attempt with these approaches to change the physicalproperties of the local tissue in order to improve the outcome.

Several surgeons have attempted to reinforce their lift procedures usingsurgical meshes in mastopexy and breast reconstruction procedures. Someof these techniques have also incorporated the use of variousreinforcing materials similar to those used in hernia repair, such asflat polymeric meshes, allografts, xenografts and autografts.

In 1981, Johnson described the use of MARLEX® (cryastallinepolypropylene) mesh to convert the support of breast tissue aftermastopexy from a cutaneous origin to a skeletal origin by attaching themesh to the area of the second rib, (Johnson, Aesth. Plast. Surg.5:77-84 (1981)). The flat MARLEX® mesh is a permanent mesh made frompolypropylene, and was implanted to provide two slings in each breastthat supported the breast tissue. It is not replaced with regeneratedhost tissue.

Auclair and Mitz have described a mesh assisted mastopexy using a flatabsorbable mesh and a periareolar skin resection technique (Auclair andMitz, Ann. Chir. Plast. Esthét. 38:107-113 (1993)). A rapidly absorbingVICRYL® mesh was placed around the anterior surface of the breast glandin order to form an internal bra.

Góes has reported the use of polyglactin 910 (an absorbable copolymer of90% glycolide and 10% L-lactide, also known as VICRYL®) and a mixed mesh(containing 60% polyglactine 910 and 40% permanent polyester) in aperiareolar mammoplasty using a double skin technique (Góes, Plast.Reconstr. Surg. 97:959-968 (1996)). The technique involves dissectingthe soft tissue envelope away from the parenchyma, and wrapping thebreast parenchyma with a mesh to help provoke the formation of avigorous connective scar to produce a breast lining structure that wouldbe less susceptible to ptosis. The soft tissue envelope is then closedaround the parenchyma. In the procedure, a dermal flap was createdaround the nipple-areolar complex, and after the lift procedure wascompleted, the dermal flap was sutured on top of the breast gland toprovide an internal cutaneous lining. The mesh was then sutured on topof the dermal flap so that it surrounded the breast gland, and the endsof the mesh were sutured together in the central part of the superioraspect of the breast to form a conical breast shape with slightelevation of the breast. Although the mesh was found to provideshort-term support, it was absorbed after 3 months. Better results werereported with the mixed (partially absorbable) mesh. The latter provideda less elastic envelope, avoided tissue displacement, and improved thequality and duration of the new breast shape (Sampaio Góes, Clin. Plast.Surg. 29:349-64 (2002)).

U.S. Pat. No. 6,210,439 to Firmin et al. discloses a circular VICRYL®mesh with a V-shaped opening extending from its center that has ametallic reinforcing wire running around the periphery. The implantassumes a conical shape suitable for mammoplasty when the reinforcingwire is tightened. However, VICRYL® mesh degrades rapidly in vivo with50% loss of strength retention at five days, no residual strength at10-14 days, and complete absorption at 42 days. This strength retentionprofile provides very little time for the formation of regenerated hosttissue that can withstand the forces exerted on the breast. In fact,Góes and Bates concluded “absorbable synthetic meshes do not persistsufficiently to have an impact on the recurrence of breast ptosis” [seeGóes and Bates, Periareolar mastopexy with FortaPerm, Aesth. Plast.Surg. 34:350-358 (2010)].

WO 2009/001293 by de Bruijn et al. also discloses permanent meshimplants for use in mesh assisted mastopexy (see also de Bruijn et al.,Aesth. Plast. Surg. 32:757-765 (2008)). These implants were performed inthe shape of oblique circular cones with the apex removed so that theycould be placed all the way around the entire breast gland with thenipple-areolar complex remaining exposed (effectively making an internalbra). The cones were made from two different non-degradable materials,polypropylene and a permanent polyester material. The results obtainedwith the softer polyester cone implants were considered to be superiorto those achieved with the more rigid polypropylene implants. In thelatter case, rippling of the polypropylene mesh in some patientsresulted in a less than satisfactory appearance, the margins of the meshwere often palpable, and in some cases extrusion of the mesh occurred.Examination of the polyester mesh removed from a patient in pain wasreported to show that the mesh appeared to possess the proper mechanicalcharacteristics necessary to reinforce a ptotic breast during mastopexy(de Bruijn et al., Plast. Reconstr. Surg. 124:364-71 (2009)).

Van Deventer et al. has also reported the use of an internal breastsupport system for mastopexy using a partially degradable mesh that wasformed into a cone by overlapping the ends of the mesh (van Deventer etal. Aesth. Plast. Surg. 36:578-89 (2012)). The mesh contained 50%polypropylene and 50% absorbable polyglactin.

A permanent implant for soft tissue support, made frompolytetrafluoroethylene (ePTFE), which can be used in forming apredetermined breast shape is disclosed by WO 2004/096098 by Hamilton etal. WO 2006/117622 by Lauryssen et al. also discloses a permanentimplant for soft tissue support of the breast that is generally L-shapedor U-shaped, but is made from polypropylene.

U.S. Pat. No. 7,476,249 to Frank discloses an implantable sling shapedprosthesis device for supporting and positioning a breast implant in apatient, wherein the device is configured from a sheet of a chemicallyinert permanent material, such as polytetrafluoroethylene or silicone,to support the breast implant. The sling shaped device provides supportto the breast but does not have shape memory that allows it to confershape to the breast or retain a three-dimensional shape.

U.S. Patent Application Publication No. 2009/0082864 by Chen et al. alsodiscloses a prosthetic device for supporting a breast implant made froma mesh. The device has a flat back wall, a concave front wall, and acurved transitional region between these walls that forms a smoothlycurved bottom periphery.

U.S. Pat. No. 7,670,372 to Shfaram et al. discloses a minimally invasivebreast lifting system. The system incorporates a biological material,such as tendons, or synthetic material, such as silicone or GOR-TEX®material (polytetrafluoroethylene), to cradle the breast.

U.S. Patent Application Publication No. 2012/0283826 by Moses et al.discloses mastopexy systems having an insertion device, a suspensionstrut, and a lower pole support. The implanted suspension strut providespole projection and attachment points for the lower pole support, andthe lower pole support can lift the lower pole of the breast.

U.S. Patent Application Publication No. 2008/0097601 by Codori-Hurff etal. discloses mastopexy and breast reconstruction procedures assisted bythe use of processed tissue material derived from intestine or dermis.The tissue material is cut to a crescent shape, and may have up to 10layers bonded together. The bonded layers can be chemicallycross-linked.

U.S. Patent Application Publication No. 2008/0027273 by Guttermandiscloses a minimally invasive mastopexy system having a soft tissuesupport sling. The latter can be made from polyethylene, PEBAX®(polyether block amide), PEEK (polyether ether ketone), nylon, PET(polyethylene terephthalate), ePTFE (polytetrafluoroethylene), silicone,or even a metal lattice. The device is designed to provide support bysuspending the breast from the upper pole region using a bone anchor.The device does not have shape memory, and does not use shape memory toconfer shape to the breast.

U.S. Patent Application Publication No. 2010/0331612 by Lashinski et al.discloses a system for performing a minimally invasive mastopexy (breastlift) that can include an elongate flexible sling used as a soft tissueanchor. The sling can be made from a mesh, and the mesh can be made, forexample, from polypropylene. The sling is designed to resist weakeningor degradation when implanted.

Notably, there is very little innovation in the design of flat meshesthat when implanted can provide a specific conformation to the inferiorsupport envelope without bunching or rippling. The problems associatedwith permanent mesh could be overcome by using an absorbable implantthat is replaced with regenerated host tissue capable of supporting thereconstructed breast. Ideally, the absorbable implant would bepre-shaped to ensure a good outcome, and for ease of use. Notably, thereare no disclosures of the use of any pre-shaped asymmetric absorbableimplants for use in mastopexy or breast reconstruction. Priordisclosures have only described symmetrical two-dimensional shapes, suchas ellipse shaped implants, which wrinkle, bunch or fold when theimplant is attached to the breast mound and the fascia (see, forexample, U.S. Patent Application Publication No. 2008/0097601 byCodori-Hurff et al.), pre-shaped hammocks and slings which aresymmetrical three-dimensional shapes that are designed to conform to thelower pole of the breast (see, for example, U.S. Pat. No. 7,476,249 toFrank which discloses an implantable sling), or pre-shaped symmetricalcone shaped implants [de Bruijn et al., Aesth. Plast. Surg. 32:757-765(2008)]. In order to make implants that conform to the anatomy of thebreast and anchor to the chest wall, the plastic surgeon needs to trim,cut, or excise material from the implant.

PCT/US2012/027975 by Galatea Corporation discloses mastopexy systems toprovide superior pole projection, to prevent ptosis recurrence, whichmay include tabs to enhance positioning.

U.S. Patent Application Publication No. 20120185041 to Mortarino et al.discloses methods for using silk meshes in breast augmentation andbreast reconstruction with a knit pattern that substantially preventsunraveling when cut. Mortarino does not disclose silk meshes with shapememory, asymmetric or three-dimensional shapes. Mortarino also does notdisclose meshes with shape memory that confer shape to a breast.

It is therefore an object of the invention to provide scaffold implantsstrong enough to support a lifted breast with or without a breastimplant wherein the scaffold allows a transition from support by theimplant to support by regenerated host tissue without any significantloss of support for the breast.

It is another object of the invention to provide implants that havesuture pullout strengths strong enough to support the weight of a breastand/or a breast augmented with a breast implant.

It is still another object of the invention to provide implants thathave a shape and design that upon placement, substantially conforms tothe breast and chest wall without buckling or bunching, and sculpts thebreast into the desired shape.

It is yet another object of the invention to provide shape memoryimplants for use in mastopexy and breast reconstruction procedures thatcan be temporarily deformed, and have the ability to spring open into athree-dimensional shape after delivery into a suitably shaped tissueplane of the body.

It is still further an object of the invention to provide shape memoryimplants for use in mastopexy and breast reconstruction procedures thatconfer shape on the breast, and can take the shape of the lower pole ofthe breast, and implants that are self-reinforced so they possess shapememory and can open into three-dimensional shapes.

SUMMARY OF THE INVENTION

Absorbable implants for use in breast surgery that are designed toconform to the breast parenchyma and surrounding chest wall have beendeveloped. These implants are designed to support newly lifted breastparenchyma, and/or a silicone breast implant. The implants have initialmechanical properties sufficient to support a breast, with or without abreast implant, and allow the in-growth of tissue into the implant asthe implant degrades. The implants also have a strength retentionprofile that allows the support of the breast to be transitioned fromthe implant to regenerated host tissue without any significant loss ofsupport for the reconstructed breast. The implants can be made frompoly-4-hydroxybutyrate (P4HB) and copolymers thereof. The implants havesuture pullout strengths that can resist the mechanical loads exerted onthe breast.

In one embodiment, the implants have a shape that: is conformable to thebreast and chest wall without causing buckling or bunching; minimizingthe need to trim the implant during surgery; and sculpturing the breastinto the desired shape.

Absorbable implants are also disclosed with shape memory. These shapememory implants can be temporarily deformed, and can be delivered byminimally invasive techniques for mastopexy and breast reconstructionprocedures. The implants can resume their preformed shapes afterdelivery into a suitably shaped tissue plane in the body. The shapedmemory implants can confer a shape to the breast. In a preferredembodiment, the absorbable implants have an asymmetric shape.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram of an asymmetric implant for breast reconstructionwith a teardrop shape and additional tabs (12, 14, 16, 18).

FIG. 2 shows a diagram of an asymmetric two-dimensional implant (95) foruse in reconstruction of the right breast with a width (W), height (H),a mid-body curved support (90), and tabs (94) to allow the implant tostretch over the breast mound without bunching.

FIG. 3 is a diagram of a split metal form (20), including an inwardlycurving half (22) and a mating outwardly curving half (28) with asemicircular groove (26) in the outlying border of the inwardly curvinghalf (28), which is used to make implants that can assume athree-dimensional shape unaided. A line in the outwardly curving half(24) designated by the letters “AA” denotes the position of across-section view (32) of the outwardly curving half of the mold (24).A material (30) to be molded is sandwiched in the split metal mold.

FIG. 4A is a diagram of a hemi-ellipsoid implant shape. FIG. 4B is aschematic of the implant with the cross-section dimensions of itsthree-dimensional shape defined by tri-axial dimensions “a”, “b” and“c”.

FIG. 5 is a diagram of an implant for breast reconstruction with a wideupper span (40) to facilitate sling support and encompass the breastmound, and an extra-large bottom tab (42) to support the breast verticalpillar and shape the IMF. The two-dimensional implant shape is designedto minimize bunching or folding of the implant during breastreconstruction.

FIG. 6 is a diagram of a two-dimensional implant for breastreconstruction designed to support the breast mound that features acurved upper line (54) to improve breast mound conformity, a short rightto left span to anchor the scaffold to the breast mound, and an oblonglower tab (50) with rounded corners to support the vertical pillar orfold under the IMF to provide shape and support to the breast.

FIG. 7 is a diagram of an implant for breast reconstruction designed tosupport the breast mound and distribute the load to specific anchoringpositions. The two-dimensional implant features a wide right to leftcurved span to provide sling support defined by width “W”, and insets(74) between anchor tabs (72 and 76) on the lower side to conform to theshape of the IMF without bunching of the implant.

FIG. 8 shows an example of a two-dimensional crescent shaped implantwith a width (W) and height (H).

FIG. 9 shows a diagram of a two-dimensional implant for breastreconstruction of width (W) and height (H¹) with a recess (110) for thenipple areola complex, an option for mid-body support (112), and tabs(116) and (118) to allow the implant to stretch over the breast moundwithout bunching.

FIGS. 10A to 10C show diagrams of a three-dimensional implant for breastreconstruction. FIG. 10A shows a partial dome shape of the implant, thatis designed to contour and add shape to the breast mound. FIG. 10B showsthe width (W) of the partial dome, and (80) shows the arch or edge ofthe dome viewed looking inside the dome. FIG. 10C shows the height (H),depth (D), and angle (θ) between the base (or floor) (84) of the partialdome and the edge (82) of the partial dome at its highest point (86).

FIGS. 11A to 11C show a three-dimensional dome shaped implant. FIG. 11Ashows a three-dimensional partial dome shaped implant (90) with threetabs (90 a, 90 b, 90 c) for breast reconstruction that is designed tocontour and add shape to the breast mound. FIG. 11B shows the width (W)of the partial dome and placement of the tabs (90 a, 90 b, 90 c). FIG.11C shows the view of the implant looking from above the partial dome.FIG. 11D shows the height (H), depth (D), and angle (θ) between the base(or floor) (92) of the partial dome and the edge of the partial dome atits highest point (94).

FIG. 12A shows an example of how a three-dimensional partial dome shapedimplant, viewed from above, can be reinforced with body ribbing (100)around the edge and body ribbing (102) in the mid-dome region (102 a and102 b) of the implant. FIG. 12B shows the same three-dimensional implantas FIG. 12A, except viewed from above and looking partially inside thedome.

DETAILED DESCRIPTION OF THE INVENTION

Ideally, it would be preferable to use an absorbable implant formastopexy and other breast reconstruction procedures that has a longerstrength retention profile, and the demonstrated ability to regeneratehealthy host tissue to support the breast. Such regenerated host tissuecould replace or reinforce the ligamentous suspension system of thebreast, acting as an artificial suspensory, and release the skin fromthe function of maintaining breast shape. The use of a prolongedstrength retention absorbable implant to provide an even suspension ofthe breast instead of using sutures would also eliminate the formationof linear stress lines associated with suture only breast lifttechniques, as well as eliminate the time required to adjust sutures tooptimize appearance. It would also be desirable to use minimallyinvasive techniques in mastopexy and breast reconstruction procedures toimplant these absorbable implants.

Furthermore, it would be desirable to provide the surgeon with a fullypre-shaped implant with shape memory and/or self-expansion capabilitythat can be temporarily deformed to allow for implantation, and thenresume its original preformed three-dimensional shape after placement ina suitably dissected tissue plane. The implant may be inserted in afolded, crimped, or constrained conformation. After insertion in asuitably shaped tissue plane, the implant would spring or open back intoan opened conformation of its own volition and due to its inherentdesign. This procedure would be somewhat analogous in technique to astandard breast augmentation procedure, wherein a small (1 to 3 inch)incision is created at the inframammary fold (IMF). This incision ismerely used by the surgeon as an access point through which the surgeondissects a much larger tissue plane into which the implant is placed bydeforming the implant and pushing it through the (small) incision.

It should be noted that such shape memory implants would differsubstantially from other implants previously disclosed for breast liftand reconstruction procedures. First, these shape memory implants wouldhave the ability to be temporarily deformed, and then to open or springinto a shape after they are delivered in vivo into a suitably shapedtissue plane. This property eliminates the need for the surgeon tounroll, for example, a flat mesh after implantation in vivo, and removewrinkles in the mesh, and also further enables minimally invasiveprocedures. Second, the shape memory implants would be designed toconfer shape to the breast unlike other implants previously disclosedthat must be shaped or draped around the breast. Third, the shape memoryimplants are not suspension devices that are suspended from the upperpole region by, for example, sutures. Fourth, the shape memory implantsare self-reinforced to allow the implants to spring into shape or deployinto an open conformation once implanted in vivo.

I. Definitions

“Absorbable” as generally used herein means the material is degraded inthe body, and the degradation products are eliminated or excreted fromthe body. The terms “absorbable”, “resorbable”, “degradable”, and“erodible”, with or without the prefix “bio”, can be usedinterchangeably herein, to describe materials broken down and graduallyabsorbed, excreted, or eliminated by the body, whether degradation isdue mainly to hydrolysis or mediated by metabolic processes.

“Bioactive agent” is used herein to refer to therapeutic, prophylacticor diagnostic agents, preferably agents that promote healing and theregeneration of host tissue, and also therapeutic agents that prevent,inhibit or eliminate infection. Agent” includes a single such agent andis also intended to include a plurality.

“Bicomponent” as generally used herein means a structure containing twoor more materials.

“Blend” as generally used herein means a physical combination ofdifferent polymers, as opposed to a copolymer formed of two or moredifferent monomers.

“Burst pressure” as used herein is determined according to ASTM D6797-02(Standard Test Method for Bursting Strength of FabricsConstant-Rate-of-Extension (CRE) Ball Burst Test) at ambient conditionsusing a ball burst fixture with a 1.6 cm circular opening and a 1 cmdiameter half-rounded probe.

“Copolymers of poly-4-hydroxybutyrate” as generally used herein meansany polymer containing 4-hydroxybutyrate with one or more differenthydroxy acid units.

“Molecular weight” as used herein, unless otherwise specified, refers tothe weight average molecular weight (Mw), not the number averagemolecular weight (Mn), and is measured by GPC relative to polystyrene.

“Poly-4-hydroxybutyrate” as generally used herein means a homopolymercontaining 4-hydroxybutyrate units. It can be referred to herein as P4HBor TephaFLEX® biomaterial (manufactured by Tepha, Inc., Lexington,Mass.).

“Shape Memory” as used herein describes a property of the implant thatallows the user to squeeze, pull, roll up, fold up, or otherwise deformthe implant temporarily in order to facilitate its insertion in the bodywherein the device recovers its preformed shape after insertion in thebody.

“Self-reinforced” as used herein describes a property of the implant inwhich the outer rim is strengthened such that the implant can besqueezed, pulled, rolled, folded, or otherwise temporarily deformed bythe user to facilitate its insertion in the body, and that allows theimplant to recover its initial shape after insertion in the body.

“Suture pullout strength” as used herein means the peak load (kg) atwhich an implant fails to retain a suture. It is determined using atensile testing machine by securing an implant in a horizontal holdingplate, threading a suture in a loop through the implant at a distance of1 cm from the edge of the implant, and securing the suture arms in afiber grip positioned above the implant. Testing is performed at acrosshead rate of 100 mm/min, and the peak load (kg) is recorded. Thesuture is selected so that the implant will fail before the suturefails.

“Taber Stiffness Unit” is defined as the bending moment of ⅕ of a gramapplied to a 1½″ (3.81 cm) wide specimen at a 5 centimeter test length,flexing it to an angle of 15°, and is measured using a Taber V-5Stiffness Tester Model 150-B or 150-E. The TABER® V-5 StiffnessTester—Model 150-B or 150-E is used to evaluate stiffness and resiliencyproperties of materials up to 10,000 Taber Stiffness Units. Thisprecision instrument provides accurate test measurement to ±1.0% forspecimens 0.004″ to 0.219″ thickness. One Taber Stiffness Unit is equalto 1 gram cm (g cm) or 0.0981 milliNewton meters (mN m). Taber StiffnessUnits can be converted to Genuine Gurley™ Stiffness Units with theequation: S_(T)=0.014195_(G)−0.935, where S_(T) is the stiffness inTaber Stiffness Units and S_(G) is the stiffness in Gurley StiffnessUnits. To convert Taber Stiffness Units to Millinewton Meters, use theequation: X=S_(T)·0.098067, where X is the stiffness in MillinewtonMeters.

II. Implants

Poly-4-hydroxybutyrate (P4HB, TephaFLEX® biomaterial) is a strong,pliable thermoplastic polyester that is biocompatible and resorbable(Williams, et al. Poly-4-hydroxybutyrate (P4HB): a new generation ofresorbable medical devices for tissue repair and regeneration, Biomed.Tech. 58(5):439-452 (2013)). Upon implantation, P4HB hydrolyzes to itsmonomer, and the monomer is metabolized via the Krebs cycle to carbondioxide and water.

U.S. Pat. No. 8,034,270 to Martin et al. discloses methods for makingcombination devices of P4HB with autologous, allogenic and/or xenogenictissues for use in mastopexy and breast reconstruction, among otherapplications. WO 2011/119742 by Martin et al. discloses PHA monofilamentand multifilament fibers coated with spin finish, and devices derivedtherefrom, including breast reconstruction devices. There is nodisclosure of specific designs for use in these procedures, norproperties of these devices that are necessary to regenerate host tissuestrong enough to support the breast and prevent recurrent ptosis. Thereis also no disclosure of shape memory designs, and designs that allowthe implant to confer shape on the breast. Moreover, there is nodisclosure of implants that retain a three-dimensional shapeirrespective of whether the implant is placed in contact with athree-dimensional part of the anatomy.

In order to prevent recurrent breast ptosis and aid in shaping thebreast parenchyma during a mastopexy or reduction procedure, implantsmade of P4HB or other materials should have strength retention timeslonger than one to two months that over time can be replaced withregenerated host tissue, and that are able to support the lifted breastmound/parenchyma (including withstanding the forces exerted by anybreast implant). The implant should: (i) have mechanical propertiessufficient to support the breast, and any breast implant, whileregenerated host tissue develops; (ii) allow predictable tissuein-growth as the implant slowly loses strength and is absorbed; (iii)have a strength retention profile that allows a transition from supportby the implant to support by regenerated host tissue without anysignificant loss of support; (iv) have a shape and design that (a) isconformable to the breast and chest wall without buckling or bunching,(b) has sufficient suture pullout strength to resist the mechanicalloads exerted on the reconstructed breast, (c) minimizes the need totrim the implant during surgery, and (d) sculpts the breast into thedesired shape; (v) optionally possess shape memory so that it can betemporarily deformed to allow for implantation and resume its originalpreformed three-dimensional shape essentially unaided; (vi) optionallyhave a 3-dimensional shape that substantially represents the shape ofthe lower pole of the breast, and (vii) optionally confer a shape to thebreast.

Absorbable implants have been developed that are comprised of scaffolds,which over time can be replaced with regenerated host tissue that isable to support a surgically revised breast (including withstanding theforces exerted by any breast implant). The implants are preferably madefrom poly-4-hydroxybutyrate or copolymer thereof. PHA fibers can beconverted into meshes and slings for breast reconstruction that allowsome fibrous tissue ingrowth, and yet are soft, supple, and barelypalpable once implanted.

The implants disclosed herein have mechanical properties that aresufficient to support the load of the breast, and the additional load ofany breast implant, while regenerated host tissue develops. Followingimplantation, the implant scaffold structure allows a predictablein-growth of tissue as the implant slowly loses strength and isabsorbed. The scaffold has a prolonged strength retention profile toensure a smooth transition from support of the breast by the implant tosupport of the breast by regenerated host tissue without any significantloss of support. As such, the implant can maintain the ideal shape ofthe operated breast that was assembled during surgery.

A major advantage of these implants over existing mesh assisted breastsurgery and specifically mastopexy is that a regenerated tissue that isstrong enough to prevent recurrent ptosis replaces the implants. Thiseliminates the problems and concerns associated with the use ofpermanent or partially absorbable meshes, such as contraction, long-termchronic inflammatory and foreign body response and allows for long-termchanges in breast volume that can result from pregnancy and weight gainor loss. The disclosed implants have major advantages over priorapproaches that have used absorbable polygalactin 910 (VICRYL®) meshes.The latter meshes undergo very rapid loss of strength in vivo, and arecompletely absorbed in about 42 days. This rapid absorption processprovides little time for a regenerated host tissue to form that cansupport the load on the breast. In contrast, the P4HB implants have aprolonged strength retention profile, and in a preferred embodiment canmaintain some residual strength for as much as one year. The prolongedpresence of these implants provides an extended period for tissuein-growth into their scaffold structures, and a residual strength toprevent early recurrent ptosis while the regenerated tissue forms.Importantly, the in-grown tissue provides strength and support beyondthe time of complete strength loss of the implant, thus demonstratingthe implant's ability to provide a durable repair beyond its absorptiontimeframe.

In an embodiment, the absorbable implants are designed so that whenmanufactured, they are flat; however, when placed around a breast, theyhave a shape that conforms to the contours of the breast and chest wallwithout causing any buckling or bunching of the implant or tissuestructures. The implants are designed to help sculpt the breast into thedesired profile, and shaped to minimize the need to trim the implantsduring surgery. In a particularly preferred embodiment, the implants areasymmetric. In contrast, absorbable meshes used in existing approacheshave generally been symmetric in shape. In a preferred embodiment, theasymmetric shaped implants are made from poly-4-hydroxybutyrate orcopolymer thereof.

In another embodiment, the implants are designed to have suture pulloutstrengths high enough to resist the initial mechanical loads exerted bythe breast, and to maintain sufficient pullout strength while tissuein-growth occurs. In contrast, polyglactin 910 (VICRYL®) rapidly losesstrength, and has negligible suture pullout strength after just a fewdays.

In a yet another embodiment, the implants are preformedthree-dimensional shapes with shape memory, designed to actively provideshape to the lower pole of the breast parenchyma. The implants can betemporarily deformed and resume their original preformed shapes afterimplantation into a suitably dissected tissue plane. The implants mayaid in conferring a shape to the breast, and are self-reinforced. In apreferred embodiment, the three-dimensional shaped implants with shapememory are made from poly-4-hydroxybutyrate or copolymer thereof.

A. Properties of the Implants

The absorbable implants have been designed to support the mechanicalforces acting on the breast during normal activities at the time ofimplantation, and to allow a steady transition of mechanical forces toregenerated host tissues that can also support those same mechanicalforces once the implant has degraded. Design of the implant includesselection of the absorbable material, and its form (such as mesh, film,foam), degree of orientation, and molecular weight. This will alsodetermine factors such as surface area and porosity. At rest, the loadexerted on a large breast weighing, for example, 1 kg, is 9.8 Newtons(N). During exercise where vertical acceleration can reach 2-3 g, or inextreme exercise peak at around 6 g, the force on the breast could riseto nearly 60 N. In a preferred embodiment, the absorbable implants canwithstand a load of at least 5 N, more preferably of at least 15 N, andeven more preferably of at least 60 N.

Since the implants are absorbable, it is beneficial that the implants bereplaced with regenerated host tissue strong enough to support thebreast. In some embodiments, it is beneficial that the implants containa porous scaffold that can allow tissue in-growth, and the formation ofa regenerated tissue strong enough to support the breast after theimplant is degraded and absorbed. In an embodiment, the scaffoldstructure of the implant has pore diameters that are at least 50 μm,more preferably at least 100 μm, and most preferably over 250 μm.

When the implant scaffold has been completely replaced by regeneratedhost tissue, it must be able to support the breast. The force per areathat the regenerated tissue needs to be able to withstand to preventrecurrent ptosis depends upon the size of the reconstructed breast,activity level of the patient, and any additional force exerted by abreast implant. In an embodiment, the regenerated tissue supporting thereconstructed breast can withstand a pressure of at least 0.1 kPa, morepreferably at least 1 kPa, and even more preferably at least 5 kPa. Inan even more preferred embodiment, the combination of the implant andthe regenerating tissue forming in the implant scaffold can alsowithstand a pressure of at least 0.1 kPa, more preferably at least 1kPa, and even more preferably at least 5 kPa.

In a particularly preferred embodiment, the absorbable implants aresutured in place. This means that although in theory the load exerted bythe breast is spread out over the implant, the entire force of thebreast tissue is shared among the points of attachment of the implant tothe body. A major advantage is that the absorbable implants disclosedherein possess a high suture pullout strength that allows a heavy breastto be supported with a limited number of anchoring sites. The highsuture pullout strength can be obtained for example, as a result ofselection of the absorbable material, molecular weight, orientation,form (such as monofilament mesh or film), and porosity.

In a preferred embodiment, a P4HB implant is anchored to the chest wallat four or more places in order to support the breast. This strategydistributes the load over multiple attachment points. In a particularlypreferred embodiment, the suture pullout strength of the absorbableimplant is greater than 10 N, and more preferably greater than 20 N.

The implant can be designed either so that it stretches equally in eachdirection, or it may stretch more in some directions than in otherdirections. The ability of the implant to stretch can allow the surgeonto place tension on the breast during implantation. However, in order tomaintain support for the breast following surgery, it is critical thatafter the implant is implanted, the implant, the regenerated hosttissue, and any transitional structures, cannot stretch significantly.In an embodiment, the implant cannot stretch more than 30% of itsoriginal length in any direction. In an even more preferred embodiment,the implants cannot stretch more than 30% of their original length inany direction and are made from poly-4-hydroxybutyrate or copolymerthereof. This property is imparted on the implant for example as aresult of the degree of orientation of the absorbable material, and alsothe weave or knit pattern if it is a textile.

It is particularly important that the surgeon is able to contour theimplant to the surface of the breast parenchyma or breast implant. It isalso desirable that the implant is not palpable through the skin onceimplanted. The implants have been designed so that they are pliable, yetcan remodel with increased in-plane stiffness over time to keep thebreast in the desired shape. In a preferred embodiment, the implants arecompliant and have a Taber stiffness that is less than 100 TaberStiffness Units, more preferably less than 10 Taber Stiffness Units, andeven more preferably less than 1 Taber Stiffness Unit. The intrinsicproperty of the absorbable material, degree of orientation andrelaxation of the polymer imparts on the implant the desired TaberStiffness.

In a particularly preferred embodiment, the implant has properties thatallow it to be delivered through a small incision. The implant may, forexample, be designed so that it can be rolled or folded to allowdelivery through a small incision. This minimally invasive approach canreduce patient morbidity, scarring and the chance of infection.

In another preferred embodiment, the implant has a three-dimensionalshape and shape memory properties that allow it to assume its originalthree-dimensional shape unaided after it has been delivered through asmall incision and into an appropriately sized dissected tissue plane.For example, the implant may be temporarily deformed by rolling it upinto a small diameter cylindrical shape, delivered using an inserter,and then allowed to resume its original three-dimensional shape unaidedin vivo. In addition, the implant may be squeezed in between the fingersto shorten the distance between the two furthest points of the implantin order to facilitate its delivery through an incision smaller than thewidth of the device.

B. Shapes

The implants can be prepared in sizes large enough to allow for theiruse in mastopexy and other breast reconstruction procedures such thatthey are wide enough to substantially span the width of a breast, andfor the surgeon to cut and trim the implants, if and as necessary, tothe required sizes and shapes. In one embodiment, the implants are cutand shaped so that they can be used in a mastopexy procedure (with orwithout a breast implant) or in any other breast reconstructionprocedure. In a preferred embodiment, the implants are pre-cut andshaped so that they will conform to the anatomical shape of thereconstructed breast. In another embodiment, the implants can be cut andshaped to reinforce breast tissues, and in particular so that there isno buckling or bunching of the implant. In still another embodiment, theimplants are two-dimensional (i.e. flat), but can be formed aroundthree-dimensional shapes without any buckling or bunching of theimplant.

In yet another embodiment, the implants are designed so that they canhelp to sculpt breast parenchyma into the desired shape. In aparticularly preferred embodiment, the implants have anatomical shapes,three-dimensional shapes, and/or asymmetric shapes. These shapesminimize the need to cut or trim the implant during use, and alsominimize any buckling or bunching of the implant.

Non-limiting examples of a support include a mesh, a set of strips, afabric, a woven construct, a non-woven construct, a knitted construct, abraided construct, a porous scaffold, a porous film including laminatedand perforated film, a nanospun, electrospun, or melt-blown construct.

The implants can incorporate one or more tabs to accommodate suturethrows or other anchoring devices for the fixation of the implant to thepatient's tissues. These tabs can be placed in order to improve theimplant's ability to conform and shape to the breast, as well as toadapt to the chest wall. In particular, these tabs can be incorporatedwith appropriate spacing into the implant so that they amplify theimplant's ability to bend and stretch around the lower curvature (lowerpole) of the breast without causing bunching, kinking, folding orwrinkling of the implant.

Asymmetric Implants

In one embodiment shown in FIG. 1, a body 10 of the asymmetric implantis shaped into a teardrop. This shape helps to prevent the implant frombuckling or bunching, minimizes the need to cut or shape the implantduring surgery, provides a low profile to avoid coverage of thenipple-areolar complex, and facilitates sculpturing the breast to createenhanced cleavage. Tabs 12, 14, 16, 18 or other shapes can also protrudefrom the teardrop, for example, to accommodate suture throws or otheranchoring devices, maximize load distributions, and further shape thecontours of the reconstructed breast. These tabs also allow the implantto contour tightly to the breast mound without forming wrinkles orfolds. In a preferred embodiment, the width to height ratio of theteardrop ranges from a ratio of 10:1 to 1.5:1, and is more preferably5:2. For example, the width (W) of the teardrop implant (shown inFIG. 1) can be about 25 cm and the height (H) of the teardrop shown inFIG. 1) can be 10-11 cm as. (The width of the teardrop is the longestdistance measured between any two points, and the height of the teardropis the longest distance measured perpendicular to the width.)

With reference to FIG. 1, four tabs are shown extending from body 10.Two tabs 12, 14 are shown extending from a base or wider portion of theteardrop, and an additional two tabs 16, 18 are shown extending from thenarrow or tip portion of the tear drop. The tabs are shown in anasymmetric arrangement. Tabs assist with contouring to the breasttissue, and providing a platform for fastening the implant to tissue.Although four tabs are shown in FIG. 1, the body 10 may include more orless than four tabs. Preferably, the implant includes at least 4 tabs.

As described herein, the implant combines various features to optimizemechanical properties. For example, various combinations of implant bodyshapes, tab shapes, tab locations, number of tabs, thickness of body,type of material, and material processing result in increased mechanicalproperties including but not limited to increased suture pull outstrength, increased breast load, increased stiffness, and increased loadafter several months (e.g. increased load after 78 weeks).

The implant may be installed in either breast. The implant shown in FIG.1 is suited for a mastopexy procedure.

In a particularly preferred embodiment, the teardrop can incorporateseam lines that can be embossed to project the two-dimensional structureof the implant into a three-dimensional structure that accentuates thebreast contouring.

In another embodiment, the asymmetric implant is shaped as shown in FIG.2, and used to reconstruct a right breast. An implant with a shape thatis the mirror image of FIG. 2 may be used to reconstruct a left breast.The implant optionally has a curved mid-body support (90) to improvebreast mound contouring and support, cut notches (92) and tabs (94) tominimize stress concentrations and allow the implant to stretch over thebreast mound with minimal bunching. The notched sections may, ifdesired, be stitched closed to create a three-dimensional cup shape. Inan embodiment, the implant has a width (W) between 22 and 30 cm, aheight (H) between 7.5 and 11 cm, a perimeter notch gap (N¹) between 0.5and 4 cm, and a tab width (N²) between 1 and 2 cm.

The implants of FIGS. 1 and 2 can be manufactured using a metal form andstandard manufacturing techniques. FIG. 3 is a diagram of a split metalform (20), including an inwardly curving half (22) and a matingoutwardly curving half (24) with a semicircular groove (26) in theoutlying border of the inwardly curving half (28), which is used to makeimplants that can assume a three-dimensional shape unaided. A line inthe outwardly curving half (30) designated by the letters “AA” denotesthe position of a cross-section view (32) of the outwardly curving halfof the mold (204). A material (210) to be molded is sandwiched in thesplit metal mold.

When the shape of the three-dimensional implant is substantially ahemi-ellipsoid, the dimensions of the implant may be defined by thetri-axial dimensions “a”, “b” and “c” shown in FIGS. 4A and 4B. In apreferred embodiment, the ranges of these dimensions are preferably “a”from 2 to 10 cm, “b” from 3 to 10 cm, and “c” from 2.5 to 12 cm.

Shaped Implants

One embodiment of a two-dimensional implant is shown in FIG. 5. Theupper region (40) of the implant has a larger footprint than the lowerregion (or tab) (46) of the implant, and is designed to support thebreast parenchyma by spreading the load to key anchoring points. Theimplant features deep in cuts (48) that allow the lower region (or tab)(42) to fold at the IMF (i.e. at the dashed line in FIG. 7) and giveshape to the IMF without bunching of the implant. The implant shown inFIG. 5 also incorporates rounded corners (e.g. (46)) to eliminate stressconcentrations in the implant. In a preferred embodiment, the width (W)of the implant shown in FIG. 5 is between 18 cm and 36 cm, and theheight (H) of the implant is between 6 cm and 14 cm.

Another embodiment of a two-dimensional implant is shown in FIG. 6. Theupper region (52) of the implant also has a larger footprint than thelower region (or tab) (50) of the implant, and is also designed tosupport the breast parenchyma by spreading the load to key anchoringpoints. Instead of incorporating deep in cuts, the implant has a curvedupper line (54) to allow the implant to conform and support the breastparenchyma without the implant bunching. The implant shown in FIG. 6also incorporates rounded corners (56) and (58) to eliminate stresses inthe implant. An oblong-shaped tab (50) allows the implant to fold at theIMF (i.e. at the dashed line in FIG. 6) and give shape to the IMF andsupport to the vertical pillar. In contrast to the implant shown in FIG.5, the implant shown in FIG. 6 has a shorter width or span from left toright to anchor the implant on the breast mound. In a preferredembodiment, the width (W) of the implant shown in FIG. 6 is between 10cm and 26 cm, and the height (H) of the implant is between 6 cm and 14cm.

A further embodiment of the two-dimensional implant is shown in FIG. 7.The implant has a curved upper line (70) (like the implant of FIG. 6) toallow the implant to conform to the breast without bunching, and a wideleft to right span (like the implant of FIG. 5) to facilitate slingsupport of the breast parenchyma. The implant has a bottom tab (76) toanchor the implant and support the breast vertical pillar, and side tabs(e.g. (72)) separated from the bottom tab (76) with inset cuts to allowthe implant to flex between tabs and form a curved IMF. The implant alsofeatures rounded corners to eliminate stress concentrations in theimplant. In a preferred embodiment, the width (W) of the implant shownin FIG. 7 is between 18 cm and 34 cm, and the height (H) of the implantis between 8 cm and 16 cm.

The implants may also be crescent-shaped, rectangular or any othershape. As a crescent shape, the implant can transition from a first lowprofile or rolled configuration to a deployed shape. The implant canalso be a canoe-like body including walls and a cavity formed therein.The cavity serves to accommodate the breast parenchyma when deployed.The implant can be configured as a sheet, a solid sheet, or as adiscontinuous layer such as a mesh.

An example of a crescent shaped implant is shown in FIG. 8. In apreferred embodiment, the crescent shaped implant has a width (W) of 10to 25.5 cm, and a height (H) of 5 to 11 cm.

Another example of an implant with an upper curving profile is shown inFIG. 9. The two-dimensional implant incorporates a recess (110) for thenipple areola complex (NAC), an option for mid-body support (112), andnotches (114) that create tabs (116) and (118) so that the implant canbe stretched over the breast mound without bunching of the implant. Thenotched sections may also be stitched closed to create athree-dimensional cup shape. The mid-body support (112) may be stitchedor embossed to create a hinge or crease. In an embodiment, the implant(900) has a width (W) between 22 and 30 cm, a height (H¹) between 8.5and 13 cm, a height (H²) between 6.5 and 11 cm, a perimeter notch gap(N¹) between 0.5 and 4 cm, and a tab width (N²) between 1 and 2 cm.

Three-dimensional Shaped Implants

The disclosed implants include embodiments with a three-dimensionalshape that is designed to provide additional predetermined contour tothe host's breast tissue or an anatomical structure of the breast. In anembodiment shown in FIG. 10, the implant has a three-dimensional partialdome shape (i.e. FIG. 10A) that allows the implant to capture, contour,and support the breast parenchyma, and distribute the load to keyanchoring positions. The ability of the implant to capture and contourthe breast parenchyma (i.e. the 3D implant mates and molds with the 3Dbreast mound) reduces surgery time. In common with the implants of FIGS.5 and 6, the implant of FIG. 10A-C has rounded corners to eliminatestress concentrations in the implant and prevent bunching of theimplant. In a preferred embodiment, the width (W) of the implant shownin FIG. 10B is between 12 and 24 cm, the height (H) measured from thefloor or base (84) of the dome to the highest point (86) shown in FIG.10C is between 2 and 10 cm, and the depth (D) of the dome shown in FIG.10C is between 2.5 cm and 10 cm. The angle θ shown in FIG. 10C ispreferably between 30° and 90°.

In a preferred embodiment, tabs may be added to the implant shown inFIG. 10A-C, for example, as shown in FIG. 11A-B. In the embodiment shownin FIG. 11A, the partial dome implant includes 3 tabs (90 a, 90 b and 90c), placed at the bottom of the implant (i.e. in the middle, 90 a) andat the right and left sides (90 b and 90 c). In a preferred embodiment,the width (W) of the implant shown in FIGS. 11A-D is between 12 and 24cm, the height (H) measured from the floor or base of the dome (92) tothe highest point (64) shown in FIG. 8D is between 2 and 10 cm, and thedepth (D) of the dome shown in FIG. 8D is between 2.5 cm and 10 cm. Theangle θ shown in FIG. 8D is preferably between 30° and 90°. Optionally,a support rib can be added to the inner surface of the partial domeimplants shown in FIGS. 10 and 11 to provide added support and, ifnecessary, rigidity, or to add shape retention to the implant (forexample, to allow minimally invasive delivery of the implant). Anexample of an implant with a three-dimensional partial dome shape thathas been reinforced with ribbing is shown in FIG. 12. In this example,the partial dome shaped implant is reinforced with body ribbing alongthe perimeter (100) of the dome and in the mid-dome (102 a and 102 b)section.

Implants with Shape Memory

The three-dimensional shaped implants disclosed herein include implantsthat have shape memory. The shape memory allows the implant to betemporarily deformed, delivered by a minimally invasive method, andresume its preformed three-dimensional shape once placed across thelower pole of the breast. A particularly preferred three-dimensionalshape comprises an outwardly curving exterior, and an inwardly curvinginterior. An even more preferred three-dimensional shape isself-reinforced and comprises an outwardly curving exterior, an inwardlycurving interior, and an outlying border that is reinforced by acontinuous or interrupted ring. The continuous or interrupted ringallows the implant to assume the desired three-dimensional shape unaidedeven if the three-dimensional shape has been temporarily deformed, forexample, by rolling it into a small diameter cylinder or manipulating itinto some other configuration. The three-dimensional shapes with shapememory may vary in shape and size. Shapes include, but are not limitedto, hemispheres, hemi-ellipsoids, domes or similar kinds of shapes. Thesizes of the three-dimensional shapes with shape memory vary, and range,for example, from a width of 8 to 20 cm at the base, more preferably 8to 17 cm at the base, and a height or radius of curvature of 5 to 10 cm.In an embodiment, the width of the three-dimensional shape is designedto be 1 to 2 cm less than the width of the patient's breast aftermastopexy. In another embodiment, the height of the three-dimensionalshape is 0.5 to 2 cm less than the patient's nipple-IMF distance aftermastopexy.

Non-limiting examples of materials that may be used to make thesethree-dimensional shaped implants with shape memory include meshes (e.g.monofilament and multifilament knitted meshes), strips, fabrics, wovenconstructs, non-woven constructs, knitted constructs, braidedconstructs, porous scaffolds, laminates, nanospuns, electrospuns, dryspuns, or melt-blown constructs, filaments, threads, strands, strings,fibers, yarns, wires, films, tapes, felts, multifilaments andmonofilaments.

C. Polymers

Any absorbable biocompatible polymer may be used to make the implantsprovided the implant has sufficient initial strength to shape andsupport the reconstructed breast, undergoes a controlled resorptionprocess in the breast, and is replaced with regenerated host tissue thatcan support the breast. The implant may, for example, be prepared frompolymers including, but not limited to, polymers of glycolic acid,lactic acid, 1,4-dioxanone, trimethylene carbonate, 3-hydroxybutyricacid, ε-caprolactone, including polyglycolic acid, polylactic acid,polydioxanone, polycaprolactone, copolymers of glycolic and lacticacids, such as VICRYL® polymer, MAXON® and MONOCRYL® polymers, andincluding poly(lactide-co-caprolactones); poly(orthoesters);polyanhydrides; poly(phosphazenes); polyhydroxyalkanoates; syntheticallyor biologically prepared polyesters; polycarbonates; tyrosinepolycarbonates; polyamides (including synthetic and natural polyamides,polypeptides, and poly(amino acids)); polyesteramides; poly(alkylenealkylates); polyethers (such as polyethylene glycol, PEG, andpolyethylene oxide, PEO); polyvinyl pyrrolidones or PVP; polyurethanes;polyetheresters; polyacetals; polycyanoacrylates;poly(oxyethylene)/poly(oxypropylene) copolymers; polyacetals,polyketals; polyphosphates; (phosphorous-containing) polymers;polyphosphoesters; polyalkylene oxalates; polyalkylene succinates;poly(maleic acids); silk (including recombinant silks and silkderivatives and analogs); chitin; chitosan; modified chitosan;biocompatible polysaccharides; hydrophilic or water soluble polymers,such as polyethylene glycol, (PEG) or polyvinyl pyrrolidone (PVP), withblocks of other biocompatible or biodegradable polymers, for example,poly(lactide), poly(lactide-co-glycolide, or polycaprolactone andcopolymers thereof, including random copolymers and block copolymersthereof. Blends of polymers can also be used to prepare the implants.Preferably the polymer or copolymer will be substantially resorbedwithin a 6 to 18 month timeframe, and retain some residual strength forat least 1-2 months, and more preferably at least 6 months.

In a particularly preferred embodiment, poly-4-hydroxybutyrate (P4HB) ora copolymer thereof is used to make the implant. Copolymers include P4HBwith another hydroxyacid, such as 3-hydroxybutyrate, and P4HB withglycolic acid or lactic acid monomer. In a preferred embodiment, theP4HB homopolymer and copolymers thereof have a weight average molecularweight, Mw, within the range of 50 kDa to 1,200 kDa (by GPC relative topolystyrene) and more preferably from 100 kDa to 600 kDa. A weightaverage molecular weight of the polymer of 50 kDa or higher is preferredfor prolonged strength retention.

D. Coatings to Stimulate Cell Attachment and In-growth

The implants can be coated, derivatized, or modified with other agentsin order to improve wettability, water contact angle, cell attachment,tissue in-growth, and tissue maturation.

In one embodiment, the implants can contain cellular adhesion factors,including cell adhesion polypeptides. As used herein, the term “celladhesion polypeptides” refers to compounds having at least two aminoacids per molecule that are capable of binding cells via cell surfacemolecules. The cell adhesion polypeptides include any of the proteins ofthe extracellular matrix which are known to play a role in celladhesion, including fibronectin, vitronectin, laminin, elastin,fibrinogen, collagen types I, II, and V, as well as synthetic peptideswith similar cell adhesion properties. The cell adhesion polypeptidesalso include peptides derived from any of the aforementioned proteins,including fragments or sequences containing the binding domains.

In another embodiment, the implants can incorporate wetting agentsdesigned to improve the wettability of the surfaces of the implantstructures to allow fluids to be easily adsorbed onto the implantsurfaces, and to promote cell attachment and/or modify the water contactangle of the implant surface. Examples of wetting agents includepolymers of ethylene oxide and propylene oxide, such as polyethyleneoxide, polypropylene oxide, or copolymers of these, such as PLURONICS®.Other suitable wetting agents include surfactants or emulsifyers.

E. Therapeutic, Prophylactic and Diagnostic Agents

The implants may contain bioactive agents.

In a preferred embodiment, the agents improve cell attachment, tissuein-growth, and tissue maturation. The implants can contain active agentsdesigned to stimulate cell in-growth, including growth factors, cellulardifferentiating factors, cellular recruiting factors, cell receptors,cell-binding factors, cell signaling molecules, such as cytokines, andmolecules to promote cell migration, cell division, cell proliferationand extracellular matrix deposition. Such active agents includefibroblast growth factor (FGF), transforming growth factor (TGF),platelet derived growth factor (PDGF), epidermal growth factor (EGF),granulocyte-macrophage colony stimulation factor (GMCSF), vascularendothelial growth factor (VEGF), insulin-like growth factor (IGF),hepatocyte growth factor (HGF), interleukin-1-B (IL-1 B), interleukin-8(IL-8), and nerve growth factor (NGF), and combinations thereof.

Other bioactive agents include antimicrobial agents, in particularantibiotics, disinfectants, oncological agents, anti-scarring agents,anti-inflammatory agents, anesthetics, small molecule drugs,anti-angiogenic factors and pro-angiogenic factors, immunomodulatoryagents, and blood clotting agents.

The bioactive may be proteins such as collagen and antibodies, peptides,polysaccharides such as chitosan, alginate, polysaccharides such ashyaluronic acid and derivatives thereof, nucleic acid molecules, smallmolecular weight compounds such as steroids, inorganic materials such ashydroxyapatite, or complex mixtures such as platelet rich plasma.Suitable antimicrobial agents include: bacitracin, biguanide,trichlosan, gentamicin, minocycline, rifampin, vancomycin,cephalosporins, copper, zinc, silver, and gold. Nucleic acid moleculesmay include DNA, RNA, siRNA, miRNA, antisense or aptamers.

Diagnostic agents include contrast agents, radiopaque markers, orradioactive substances which may be incorporated into the implants.

The implants may also contain allograft material and xenograftmaterials. In yet another preferred embodiment, the implants mayincorporate systems for the controlled release of the therapeutic orprophylactic agents.

II. Methods of Manufacturing Implants

A variety of methods can be used to manufacture the implants, and theirscaffold structures. The methods must, however, allow the constructionof implants that can: (i) withstand a load of at least 5 N, (ii) supporta pressure of at least 0.1 kPa, and (iii) hold a suture with a pulloutstrength exceeding 10 N. In one embodiment, the porous scaffolds areprepared using a process that incorporates particulate leaching. Thisprocess allows the size and porosity of the scaffold to be controlled bycareful selection of the size of the leachable material and itsdistribution. The scaffolds can be prepared by dispersing particles ofthe leachable material in a solution of a biocompatible absorbablepolymer, wherein the leachable material is not soluble in the polymersolvent. In a preferred embodiment, the leachable particle materialshave a diameter of at least 25 μm, and more preferably greater than 50μm. The leachable particles must be non-toxic, easily leached from thepolymer, non-reactive with the polymer, and biocompatible (in caseresidues are left in the scaffold after leaching). In a preferredembodiment, the leachable particles are water soluble, and can beleached from the polymer solution with water. Examples of suitableparticles include salts such as sodium chloride, sodium citrate, andsodium tartrate, proteins such as gelatin, and polysaccharides such asagarose, starch and other sugars. Examples of suitable solvents for thepolymers include tetrahydrofuran, dioxane, acetone, chloroform, andmethylene chloride. In a particularly preferred embodiment, an implantcomprising a porous scaffold is formed from P4HB by adding saltparticles (100-180 μm diameter) to a solution of the polymer indioxanone (10% wt/vol), allowing the solvent to evaporate, pressing themixture using a hydraulic press with heated platens, and leaching outthe salt particles after the polymer has crystallized.

In another embodiment, a process that includes phase separation is usedto form the porous scaffold. The size of the pores can be selected byvarying parameters such as the solvent, and the concentration of thepolymer in the solvent. Suitable solvents include tetrahydrofuran,dioxane, acetone, chloroform, and methylene chloride. In a particularlypreferred embodiment, a cast solution of P4HB dissolved in dioxane (3%wt/vol) is frozen at −26° C. to precipitate the polymer, and the solventsublimated in a lyophilizer to form a phase separated porous P4HBscaffold.

In a further embodiment, the scaffolds can be prepared from films. Thefilms are made by either solvent casting or melt extrusion. The filmscan be un-oriented, or more preferably oriented in one or moredirections so that they have sufficient mechanical properties to supportthe breast, and provide prolonged strength retention. In order to allowtissue in-growth, the films must be rendered porous or attached to otherporous components. Suitable methods for making the films porous includepunching or laser drilling holes in the films, or cutting slits or holesin the films. In a particularly preferred embodiment, porous scaffoldsare prepared by melt extrusion of P4HB films, and holes are cut, punchedor drilled in the films.

In still another embodiment, the scaffold can comprise thermally bondedfibers. The thermally bonded fibers can be produced by melt extrusionusing a multi-holed die. This process allows the diameter of the fibers,the porosity of the scaffold, and the thickness of the scaffold to becontrolled by selection of parameters such as the diameter of the dieholes, the distance between the die and collector plate, and thecollection time. In a preferred embodiment, the thermally bonded fiberscaffold has one or more of the following properties (i) a thickness of0.1-5 mm, (ii) an areal density or basis weight of 5 to 800 g/m², (iii)a suture pullout strength of greater than 10 N, and (iv) is able towithstand a pressure of at least 0.1 kPa. In a preferred embodiment, thescaffold is formed from thermally bonded P4HB fibers.

The scaffolds can also be formed from structures comprising non-wovensthat have been prepared by entangling fibers using mechanical methods.The properties of the nonwovens can be tailored by selection ofparameters such as fiber diameter, fiber orientation, and length of thefibers (for staple nonwovens). In a preferred embodiment, the scaffoldscomprising non-wovens have one or more of the following properties (i) athickness of 0.1-5 mm, (ii) an areal density of 5 to 800 g/m², (iii) asuture pullout strength of greater than 10 N, and (iv) is able towithstand a pressure of at least 0.1 kPa. In a preferred embodiment, thescaffold is formed from a P4HB non-woven.

The scaffolds may also be formed directly from solution by spinningprocesses. In these processes, solutions are pumped or forced throughdies, and fibers are collected after removal of the polymer solvent. Thefiber diameters and porosities of the scaffolds can be controlled byappropriate selection of parameters such as the solvent, temperature,pump pressure or force, die configuration, and the diameter of the holesin the die. In the case of wet spinning, the choice of coagulationnon-solvent may be used to control fiber diameter and scaffold porosityand morphology. In a preferred embodiment, the solution spun scaffoldshave (i) a thickness of between about 0.5 and 5 mm, (ii) a weight ofbetween 5 and 800 g/m², (iii) a suture pullout strength of greater than10 N, and (iv) are able to withstand a pressure of at least 0.1 kPa. Ina preferred embodiment, the scaffold is formed from solution spun P4HBfibers.

In yet another embodiment, the scaffolds can be prepared frommonofilament fibers, multifilament fibers, or a combination of thesefibers. Melt extrusion and solution spinning processes can be used toform these fibers. In a preferred embodiment, the scaffolds are woven orknitted from the pre-formed fibers. The scaffolds may be produced byeither warp or weft knitting processes, however, a warp knit ispreferred in order to minimize the stretching of the scaffold structure.In a preferred embodiment, the scaffold woven from mono or multifilamentfibers has one or more of the following properties: (i) stretches lessthan 30% of the scaffold's original length in any direction, (ii) has asuture pullout strength of at least 10 N, and (iii) can withstand apressure of at least 0.1 kPa. In a particularly preferred embodiment,the scaffold is made from P4HB monofilament fibers, P4HB multifilamentfibers, or a combination of these fibers, and has an areal density of 5to 800 g/m². The implant can also be prepared by combining a woven orknitted P4HB construct with a P4HB film.

In still another embodiment, the scaffolds may be prepared by methodsthat include 3D printing (also known as additive manufacturing). Thismethod is particularly useful in the manufacture of specific shapessince the desired shape can be made directly without the need forfurther cutting or trimming.

In still a further embodiment, the scaffolds may be prepared by molding.In these processes, polymer may be directly molded into a scaffold, orthe polymer may be first converted into another form (such as a mesh,film, non-woven, laminate, electrospun fabric, foam, thermoform orcombinations thereof), and then the form molded, or two methods may beused to form a scaffold that has varying stiffness. In a preferredembodiment, three-dimensional shapes with shape memory are prepared bymolding a monofilament mesh into a shape designed to confer shape to thehost's breast tissue or form an anatomical shape of the breast. Suchshapes include those with an outwardly curving exterior and inwardlycurving interior, and optionally contain an outlying border that isreinforced by a continuous or interrupted ring that allows thethree-dimensional scaffold to be temporarily deformed and resume athree-dimensional shape. (Such shapes have shape memory.) Shapes withoutwardly curving exteriors and inwardly curving interiors may, forexample, be prepared using a split metal form consisting of an inwardlycurving half and a mating outwardly curving half as shown in FIG. 3. Oneskilled in the art will understand that the size and shape of the splitmetal form can be varied in order to provide different three-dimensionalshapes that can confer shape to a patient's breast. In a preferredembodiment, the inwardly curving half of the metal form contains asemicircular groove in the outlying border that will accommodate acontinuous or interrupted ring of filament, thread, strand, string,fiber, yarn, wire, film, tape, tube, fabric, felt, mesh, multifilamentor monofilament. In a particularly preferred embodiment the groove willaccommodate a monofilament, preferably a monofilament extrudate. Thesemicircular groove is cut into the outlying border of the inwardlycurving half such that the ring of material, for example, amonofilament, will protrude from the groove. In an alternativeembodiment, the groove may be cut into the outwardly curving halfinstead of the inwardly curving half. A three-dimensional shape with aninwardly curving interior, outwardly curving exterior, and reinforcedoutlying border is prepared by placing, for example, a filamentous orother extrudate in the semicircular groove of the inwardly curving halfso that it forms a ring, draping a polymeric material such as amonofilament mesh over the inwardly curving half of the metal form,placing the mating outwardly curving half of the metal form over thepolymeric material, and clamping the two halves of the split metal formtogether to form a block. The block is then heated, cooled,disassembled, and the three-dimensional shape removed and trimmed asnecessary to form a smooth outlying border. In an embodiment, the blockis heated uniformly, preferably by heating with hot water, and cooleduniformly, preferably by cooling with ambient temperature water. In apreferred embodiment, the three-dimensional shape is made from apoly-4-hydroxybutyrate monofilament mesh, and a poly-4-hydroxybutyratemonofilament extrudate. The temperature of the hot water is set suchthat the ring is either pressed or melted into the outlying border toreinforce the outlying border. When the three-dimensional shape is madefrom poly-4-hydroxybutyrate, the temperature of the hot water is set atapproximately 56° C., and the polymer construct is heated forapproximately 5 minutes. We have discovered that provided a ring ofpolymer, derived, for example, from a poly-4-hydroxybutyratemonofilament extrudate, is used to reinforce the outlying border of thepoly-4-hydroxybutyrate scaffold, the scaffold can be temporarilydeformed for implantation, and will then resume its three-dimensionalshape when released in a suitably dissected tissue plane. However, if aring is not used to reinforce the edge of the poly-4-hydroxybutyratematerial (such as a monofilament mesh), the poly-4-hydroxybuyratematerial will not be able to resume a three-dimensional shape.

In another embodiment, the implants comprise retainers, such as barbs ortacks, so that the implant can be anchored to the chest wall without theuse of additional suture. For example, the three-dimensional implantsmay contain retainers in their outlying borders to anchor the implants.

The implants can be cut or trimmed with scissors, blades, other sharpcutting instruments, or thermal knives in order to provide the desiredshapes. The implants can also be cut into the desired shapes usinglaser-cutting techniques. This can be particularly advantageous inshaping fiber-based implants because the technique is versatile, andimportantly can provide shaped products with sealed edges that do notshed cut loops or debris produced in the cutting process.

The processes described herein to produce the scaffolds can also be usedin combination. For example, a woven construct could be combined with anon-woven construct to make a scaffold. In a preferred embodiment, ascaffold can be reinforced with a monofilament or multifilament fiber.In a particularly preferred embodiment, the implants can be reinforcedat anchor points to provide, for example, increased suture pulloutstrength.

III. Methods of Implanting

The implants are most suited to use in mastopexy or mastopexyaugmentation procedures, wherein the skin of the lower pole is dissectedaway from the breast and eventually tightened to provide a moreappealing breast contour. However, the implants may also be used inother procedures such as revision procedures following the removal of abreast implant, and breast reconstruction procedures followingmastectomy, particularly where it is desirable to retain the position ofa silicone or saline breast implant or tissue expander. For example, theimplants may be used on the lateral side of a patient's breast toproperly retain a breast implant, or to cover a breast implant. Theimplants may also be used in conjunction with expanders in breastreconstruction procedures to give additional support for the skinsurrounding an expander, and to create a pocket for a breast implant.They may also be implanted to cover any defects in the major pectoralismuscle, after insertion of breast implants, in patients undergoingbreast reconstruction where the muscle has been compromised as a resultof breast cancer and mastectomy.

Any current mastopexy technique may be used to achieve a breast liftwith the implants using any appropriate skin resection pattern, providedit preserves the functional integrity of the mammary structures. Theimplants can also be implanted using minimally invasive techniques suchas those disclosed by U.S. Patent Application No. 20120283826 to Moseset al.

The chosen method will depend upon the extent of breast ptosis and anumber of other factors. The four main techniques for mastopexy are the:crescent mastopexy, donut (or Benelli) mastopexy, lollipop (or vertical)mastopexy, and anchor (or Weiss or Wise) mastopexy. In the crescentmastopexy, a semi-circular incision is made on the upper side of theareolar, and a crescent shaped piece of breast tissue removed. Thisprocedure is typically used for patients with only mild ptosis where agood lift can be achieved by removing excess skin on the upper breast,and suturing the skin back in order to elevate the areolar nipplecomplex. In one embodiment, the implants can be implanted after furtherdissection and/or resection to provide additional support for the upperbreast tissue.

The implants can also be implanted during a donut or Benelli mastopexy.In this procedure, a donut shaped piece of breast skin is removed fromaround the areolar with an inner incision line following the perimeterof the areolar, and an outer incision line circling the areolar furtherout. In one embodiment, the implant(s) can be inserted after furtherdissection to support the lift, and a purse string suture used toapproximate the breast skin back to the areolar.

In both the lollipop and anchor mastopexy procedures, incisions are madearound the areolar complex. In the lollipop procedure, a verticalincision is made in the lower breast from the areolar to theinframammary fold, and in the anchor mastopexy procedure an incision ismade across the inframammary fold in addition to the vertical incisionused in the lollipop procedure. The lollipop procedure is generally usedfor patients with moderate ptosis, whereas the anchor procedure isnormally reserved for patients with more severe ptosis. These twoprocedures can be performed with or without breast implant augmentation.In both procedures, breast tissue may be resected, and the resectededges sutured together to create a lift. Prior to suturing the resectedtissue, the implants can be implanted to support the breast, and todecrease the forces on the resected skin and suture line after closure.In a particularly preferred procedure, the implants are positioned tosupport the breast parenchyma or implant, and to minimize the weight ofthe breast on the skin and suture line. In an even more preferredprocedure, the suture line is closed with minimal or no tension on thewound to minimize scar formation.

In a preferred embodiment, when sutured in place, the implants providesupport, elevation and shape to the breast by anchoring of the implantsat one or more locations to the tissue, muscle, fascia or the bones ofthe chest or torso. In a particularly preferred embodiment, the implantsare sutured to the pectoralis fascia or the clavicle. The implants mayalso be sutured to the chest wall or fascia, and in a particularlypreferred embodiment, the implants may be sutured to the chest wall sothat they provide slings for support of the lifted breast or breastimplant.

The teardrop implant of FIG. 1 is designed to be implanted with thewider section positioned medially for primary load support, and thetapered section positioned on the side of the chest near the arm forlateral support and to direct the breast to the cleavage area. Thus in apreferred embodiment, the implant is asymmetric, and has a precisegeometric form. The implant may be anchored first in the medial positionusing the two suture tabs located in the wider section of the implant,and then the tapered end of the implant subsequently anchored,preferably under tension. Tabs are shown in FIG. 1 having a length towidth ratio ranging from about 1:1 to 1:2. However, the shape and sizeof the tabs may vary widely and are only intended to be limited asrecited in the appended claims.

In a preferred embodiment, the three-dimensional implants with shapememory are implanted using minimally invasive techniques into a suitablydissected tissue plane to confer shape to the breast. These implantsmay, for example, be rolled up into a small cylindrical shape, placedinside a tubular inserter, and implanted through a small incision, suchas a standard size incision at the inframammary fold that is usuallyused for breast augmentation. Once released in vivo, these implants willresume their original three-dimensional shapes, and may be moved intoposition, for example, to confer shape to the host's breast tissue or ananatomical shape of the breast. In one preferred embodiment, the implantis delivered by employing an IMF incision used as the entry point fordissection, along with a periareolar incision, in a mastopexy procedure.Once skin removal and dissection is complete, a three-dimensional shapememory implant can be deployed in vivo and allowed to resume itspreformed three-dimensional shape. The relative rigidity of theself-reinforcing three-dimensional implant allows the implant to remainin place. One skilled in the art will appreciate that thesethree-dimensional implants can also be delivered by other minimallyinvasive methods as well as using more traditional open surgerytechniques.

The present invention will be further understood by reference to thefollowing non-limiting examples.

EXAMPLE 1 Regeneration of Tissue from a Bicomponent P4HB Implant

Materials and Methods

A bicomponent P4HB absorbable implant was prepared from a thin 60 μmthick extruded film of P4HB and a knitted P4HB monofilament constructwith average pore diameter of approx. 500 μm and an areal density ofapprox. 182 g/m². The film was bonded to the mesh by ultrasonicallywelding the layers together using small pieces of P4HB extrudate(approx. OD 1.5 mm, length 1.27 mm) as a binder. The welding wasperformed using a model 2000× Branson ultrasonic welder with a 5×5 inchhorn and a flat metal anvil. The knitted construct was placed on theanvil and pieces of the extrudate were placed on the knitted material ata spacing of about 13 to 19 mm. The film was then positioned so that thepieces of extrudate were between the film and knitted materials. Thehorn was lowered and the layers were welded together with a burst ofultrasonic energy (weld energy 100 J, 0.5 s, amplitude 90% fixed, 0.21MPa pressure). The molecular weights (Mw) of the film and knittedmaterials relative to polystyrene were 313 kDa and 305 kDa,respectively.

Six samples of the P4HB implant (51×51 mm) were implanted subcutaneouslyin the backs of New Zealand white rabbits. A total of 17 rabbits wereimplanted; three rabbits for 4, 12 and 26 weeks, and four rabbits for 52and 78 weeks. Following explanation, one explant from each rabbit waskept for histological analysis and the remaining explants (n=5 peranimal) were used for mechanical and molecular weight testing. A totalof 15 samples were received and analyzed for the 4, 12, 26 and 78-weektime points, while 20 samples were received and analyzed at 52 weeks.The mechanical testing data is summarized in Table 1.

Results

The bicomponent implant had a thickness of 0.613 mm, and the knittedstructure had an average pore diameter of approx. 500 μm. The burstpressure of the implant was approximately 3.09 MPa.

As noted in Table 1, a portion of the 52 and 78-week explants weretested as received and were observed to have higher than expected burstvalues (i.e. the average burst value at 52 weeks is higher than the 26week value, while the value at 78 weeks is similar to that at 26 weeks).This is the result of the presence of in-grown, attached tissue addingto the bursting pressure of the combined tissue/P4HB explant. When theremaining explants at 52 weeks were treated with collagenase (noted as“enzyme” in Table 1) to remove the ingrown, attached tissue, manysamples of the P4HB implant were found to have degraded significantlyand were unsuitable for mechanical testing (n=9). The average burstpressure value (0.17 MPa) of these intact samples (n=5) remaining at 52weeks after enzyme digestion is recorded in Table 1. After 78 weeks,none of the enzymatically digested samples were suitable for mechanicaltesting so burst pressure at 78 weeks was only recorded for as receivedsamples (i.e. without enzyme digestion). It should be noted that the 4,12 and 26-week explants were only tested as received (i.e. withoutenzyme digestion), and that the P4HB film became rapidly porous and wasquickly degraded.

The data in Table 1 demonstrate that the P4HB implant is replaced invivo by regenerated host tissue with a significant burst pressure thatis more than sufficient to support a reconstructed breast. At 78 weeks,the average burst pressure of the as received explants was 0.98 MPa,while the enzymatically digested explants demonstrated that the originalP4HB implant did not contribute to the burst pressure and wassubstantially degraded. At 52 weeks, the P4HB implant was also found tobe significantly degraded with the enzymatically degraded P4HB implanthaving a residual burst pressure of just 0.17 MPa. In contrast, theexplants at 52 weeks that had not been enzymatically digested had anaverage burst pressure of 1.47 MPa. This means that at 52 weeks, themajority of the burst pressure is due to the tissue, rather than theP4HB implant, and at 78 weeks all the burst pressure is due to theregenerated tissue.

TABLE 1 Properties of Implant over Time after Digestion Implant TimeBurst Pressure (wks) # Tested (n) MPa % Strength Retention  0 4 3.08 100 4 15 2.37 77 12 15 1.39 45 26 15 1.11 36 52 5 0.17 5 enzyme digested 526 1.47 48 as received 78 6 0 ND enzyme digested 78 9 0.98 32 as received

EXAMPLE 2 Regeneration of Tissue from a P4HB Implant of Thermally BondedFibers

Materials and Methods

A P4HB implant was prepared from thermally bonded fibers of P4HB with athickness of approximately 1 mm, an areal density of 260 g/m², and aweight average molecular weight relative to polystyrene of 129 kDa. Theburst pressure of the P4HB implant was 0.91 MPa, and the pore size ofthe implant was approximately 50 μm.

Results

The P4HB implants were implanted subcutaneously in the backs of NewZealand white rabbits for 2, 4, 8, 12 and 24 weeks. The ability of theP4HB implants to regenerate host tissue with significant burst pressurewas determined. The mechanical testing and molecular weight data for theexplants are summarized in Table 2. In contrast to Example 1, none ofthe explanted samples were enzymatically digested with collagenase formechanical testing because the thermally bonded fibers of the P4HBimplant were found to degrade very rapidly. As shown in Table 2, norecoverable P4HB polymer could be found at the 26-week time point, andtherefore the molecular weight of the polymer could not be determined atthis time point. All the values shown in Table 2 are for the burstpressure of the as received explants, and are therefore composite valuesof the residual P4HB implant and the ingrown tissue.

As shown in Table 2, the burst pressure of the explanted samplesinitially decreased during the first 8 weeks, but then began to increaseuntil the burst pressure reached approx. 0.96 MPa at 26 weeks. This datashows that the P4HB implant can be replaced by regenerated host tissuein vivo, and that the new tissue would be able to support a significantload in a reconstructed breast.

TABLE 2 Properties of Implant over Time Burst Mw Pressure % StrengthTime (wk) (kDa) MPa Retention 0 129 0.91 100 2 123 0.69 76 4 111 0.65 728 95 0.43 47 12 83 0.46 50 26 NA 0.96 105

EXAMPLE 3 Preparation of an Asymmetric Shaped P4HB Implant

A teardrop shaped P4HB implant having the dimensions and shape shown inFIG. 1 was prepared from a knitted P4HB monofilament structure with apore diameter of approximately 500 μm, thickness of 0.5 mm, arealdensity of approx. 182 g/m², suture pullout strength of 5.6 kgf, and aburst pressure of 3.06 MPa. The implant was cut to the desired shapewith scissors.

EXAMPLE 4 Minimally Invasive Delivery of a Two-dimensional P4HB ImplantMinimizing Buckling and Bunching of the Implant Upon Placement

A minimally invasive dissection was performed on a cadaver wherein twosmall (2 inch) incisions were created in standard entry points: aperiareolar incision and an inframammary fold incision. This wasfollowed by blunt dissection separating the breast parenchyma from theskin to create a tissue plane from the medial to the lateral sides ofthe lower pole of the breast. A two-dimensional shaped implant wasrolled into a small diameter cylinder, and placed inside an insertiondevice suitable for deployment of the implant in vivo. The implant wasdeployed from the insertion device, and placed to confer shape to abreast with minimal buckling and bunching of the implant.

EXAMPLE 5 Preparation of a P4HB Implant Comprising a Three-dimensionalScaffold Designed to Confer Shape to a Breast, or Anatomical Shape of aBreast, Wherein the Three-dimensional Shape can be Temporarily Deformedto Allow for Implantation, and Resume its Three-dimensional Shape afterImplantation

A split metal mold consisting of an inwardly curving half and a matingoutwardly curving half was prepared, with a semicircular groove placedin the outlying border of the inwardly curving half, as shown in FIG. 3.A P4HB monofilament extrudate was cut to length, and pushed into thesemicircular groove with part of the monofilament protruding from thegroove. A knitted P4HB monofilament mesh, measuring approx. 15×20 cm,with a pore diameter of approximately 500 μm, thickness of 0.5 mm, arealdensity of approx. 182 g/m², suture pullout strength of 5.6 kgf, and aburst pressure of 3.06 MPa, was draped over the entire surface of theinwardly curving half of the metal form and the monofilament in thesemicircular groove. The mating outwardly curving metal form was gentlyplaced over the mesh, and the two halves of the split metal mold wereclamped together to form a block. The block was uniformly heated on allsides by placing the block in hot water maintained at 56° C. for 5minutes. The block was then uniformly cooled for 1 to 2 minutes byplacing the block into a water bath at ambient temperature. The blockwas disassembled, and the mesh shape gently lifted from the metal mold.Unwanted compressed extrudate was removed from the implant by trimmingthe outlying border.

COMPARATIVE EXAMPLE 5 Preparation of a P4HB Implant from a Scaffold witha Three-dimensional Shape without a Reinforced Outlying Border

A split metal mold consisting of an inwardly curving half and a matingoutwardly curving half was prepared, but without a semicircular grooveplaced in the outlying border of the inwardly curving half (as describedin Example 4). A knitted P4HB monofilament mesh, measuring approx. 15×20cm, with a pore diameter of approximately 500 μm, thickness of 0.5 mm,areal density of approx. 182 g/m², suture pullout strength of 5.6 kgf,and a burst pressure of 3.06 MPa, was draped over the entire surface ofthe inwardly curving half of the metal form. The mating outwardlycurving metal form was gently placed over the mesh, and the two halvesof the split metal mold were clamped together to form a block. The blockwas uniformly heated on all sides by placing the block in hot watermaintained at 56° C. for 5 minutes. The block was then uniformly cooledfor 1 to 2 minutes by placing the block into a water bath at ambienttemperature. The block was disassembled, and the three-dimensional meshgently lifted from the metal mold. Unwanted mesh was removed from theimplant by trimming.

EXAMPLE 6 Minimally Invasive Delivery of a Three-dimensional P4HBImplant with a Reinforced Outlying Border

The implant prepared in Example 5 (and with a reinforced outlyingborder) was rolled into a small diameter cylinder, and placed inside aninsertion device suitable for deployment of the implant in vivo. Theimplant assumed its original three-dimensional shape when the implantwas deployed from the insertion device.

COMPARATIVE EXAMPLE 6 Attempted Minimally Invasive Delivery of aThree-dimensional P4HB Implant without a Reinforced Outlying Border

The implant without a reinforced outlying border prepared in ComparativeExample 5 was rolled into a small diameter cylinder, and placed insidean insertion device suitable for deployment of the implant in vivo. Theimplant failed to assume its three-dimensional shape unaided when theimplant was deployed from the insertion device. This exampledemonstrates the need to self-reinforce the outlying border of a P4HBimplant in order for the implant to have shape memory and be able toconfer shape to a breast.

Modifications and variations of the methods and compositions will beapparent from the foregoing detailed description and are intended tocome within the scope of the appended claims.

We claim:
 1. An implant for plastic surgery procedures comprising anabsorbable porous polymeric scaffold formed into an anatomical shape,two-dimensional shape, three dimensional shape or asymmetric shape, withan areal density between 5 and 800 g/m² and an absorbable outlyingborder element along the perimeter of the scaffold.
 2. The implant ofclaim 1 wherein the outlying border is a continuous ring.
 3. The implantof claim 1 comprising a predetermined three dimensional shape selectedfrom a partial dome and canoe-like shape.
 4. The implant of claim 1wherein the implant has one or more properties selected from the groupconsisting of: an inwardly curving interior; a width ranging from 12-24cm; at least three tabs radially extending from the body of the implant;rounded corners; does not stretch more than 30% of its original length;a height ranging from 2 to 10 cm and at least one retainer.
 5. Theimplant of claim 4 wherein at least one of the tabs has a width rangingfrom 1 to 2 cm.
 6. The implant of claim 4, comprising a height 0.5 to 2cm less than a nipple to inframammary fold distance after mastopexyand/or a width 1 to 2 cm less than a width of the patient's breast aftermastopexy.
 7. The implant of claim 1 wherein the scaffold comprises amesh comprising poly-4-hydroxybutyrate.
 8. The implant of claim 7wherein the mesh comprises a blend of polymers.
 9. The implant of claim1 wherein the implant has a suture pullout strength greater than 10 N.10. The implant of claim 1 wherein the implant has a bending stiffnessless than 100 gram cm (100 Taber Stiffness Units).
 11. The implant ofclaim 1 wherein the implant can be rolled into a cylindrical shape andresume the three dimensional shape unaided.
 12. The implant of claim 1wherein the scaffold comprises a knitted mesh, fabric, woven construct,non-woven construct, braided construct, porous scaffold, porous film,laminate, nanospun, electrospun, or melt-blown construct.
 13. Theimplant of claim 1 wherein the implant has a strength retention timegreater than one month, wherein the strength retention is measured aspercent of burst pressure of an explanted implant after one monthcompared to its original burst pressure.
 14. The implant of claim 12produced by a method comprising the steps of: (a) placing a shape memorycomponent material selected from the group consisting of a filament,thread, strand, string, fiber, yarn, wire, film, tape, tube, fabric,felt, mesh, multifilament, or monofilament in the semicircular groove ofa first metal mold so that it forms a ring, wherein the first splitmetal mold comprising two halves and a semicircular groove in one halfof the mold; (b) placing a mesh between the two halves of the firstsplit mold, and clamping the two halves of the split metal mold togetherto form a block; (c) heating the block at a temperature between 50° C.and 70° C. cooling the block at a temperature between 0° C. and 25° C.disassembling and removing a molded shape from the block; (d) cuttingthe molded shape to remove unwanted shape memory material and meshcomponent; (e) placing the cut molded shape form in a second split metalmold consisting of an inwardly curving half and an outwardly curvinghalf; (f) clamping the inwardly curving and outwardly curving halves ofthe mold together to form a block; (g) heating the block at atemperature between 40° C. and 52° C.; and (h) cooling the block at atemperature between 0° C. and 25° C.
 15. The implant of claim 14,wherein the mesh has one or more properties selected from the groupconsisting of a pore diameter of 500 μm or more, a thickness of 0.5 mm,an areal density of approx. 182 g/m², and a burst pressure of 3.06 MPa.16. The implant of claim 14 wherein the mesh is a knitted P4HBmonofilament mesh.
 17. The implant of claim 16, comprising 4, 5, 6, 7 or8 tabs.
 18. The implant of claim 17, wherein the tabs have a length towidth ratio ranging from about 1:1 to 1:2.
 19. The implant of claim 16,wherein the implant has a strength retention of about 50% at 12 weeksfollowing implantation.
 20. The implant of claim 1, wherein thepolymeric scaffold and outlying border are made from the same polymer.21. The implant of claim 14, wherein the mesh comprises oriented polymerand the outlying border comprises unoriented polymer.